Based on the theory of a regional disaster system and data from the Yunnan region from 1991 to 2015, this article constructs an index system for assessing the integrated loss of earthquake-flood disaster, which is the hazard and the vulnerability of hazard-bearing bodies. A dynamic spatial panel model for integrated loss assessment of earthquake-flood disaster is established. The results show that there are significant positive spatial spillover effects and time lag effects in the integrated loss of earthquake-flood disaster, and the coefficient of integrated hazard is estimated to be 0.7183, which is 3.7 times the integrated vulnerability index. It has a greater effect on the integrated loss. From the determination coefficient R2, logarithmic likelihood value logL and the t value of coefficient significance test, the model is used to explain the loss change, and the integrated loss level of the whole earthquake-flood disaster in Yunnan is higher. The assessment results have important theoretical and practical significance for integrated disaster prevention and mitigation.